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Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience

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Abstract

Purpose

We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).

Methods

A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100 %), chemotherapy (61 %), and hepatic chemoembolization (50 %). Patients received capecitabine at 600 mg/m2 orally twice daily on days 1–14 (maximum 1,000 mg orally twice daily) and TMZ 150–200 mg/m2 divided into two doses daily on days 10–14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle.

Results

Using RECIST parameters, 1 patient (5.5 %) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5 %) achieved a partial response (PR), and 4 patients (22.2 %) had stable disease (SD). Total response rate was 61 %, and clinical benefit (responders and SD) was 83.2 %. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3–18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28–140 months). The only grade 3 toxicity was thrombocytopenia (11 %). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths.

Conclusions

CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.

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Acknowledgments

We want to thank Kindra Matthews who helped in the assembly of this manuscript. We also thank the following physicians for their continued support and patient referral: Vilma Rosario, William Isacoff, Andrew Pecora, M. Wasif Saif, and Douglas Fraker. This paper is dedicated posthumously to the life and work of Peter D. Stevens, MD. His colleagues at The Pancreas Center at Columbia are in debt and gratitude to his brilliant leadership and vision. This research was funded by The Chemotherapy Foundation, The Sackler Foundation, and The Sol Berg Foundation. A special thanks to Schering Plough/Merck for supplying Temodar (temozolomide) to our patients as well as for their continued support and guidance throughout this study.

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Authors and Affiliations

  1. Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at Columbia, New York Presbyterian-Columbia University Medical Center, William Black Research Building, Room 20-05, 650 West 168th Street, New York, NY, 10032, USA

    Robert L. Fine, Anthony P. Gulati, Benjamin A. Krantz, Dawn A. Tsushima, Kelley B. Mowatt, Richard D. Dinnen, Yuehua Mao & William H. Sherman

  2. Division of Medical Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, UMDNJ, New Brunswick, NJ, USA

    Rebecca A. Moss

  3. Hematology-Oncology Associates, Carol Simon Cancer Center, Morristown Memorial Hospital, Morristown, NJ, USA

    Stephen Schreibman

  4. Division of Gastroenterology, Endoscopic and Interventional Service, The Pancreas Center at Columbia, New York, NY, USA

    Peter D. Stevens

  5. Division of Gastrointestinal and Endocrine Surgery, The Pancreas Center at Columbia, New York, NY, USA

    Beth Schrope, John Allendorf, James A. Lee & John A. Chabot

Authors
  1. Robert L. Fine
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  2. Anthony P. Gulati
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  6. Dawn A. Tsushima
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  8. Richard D. Dinnen
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  9. Yuehua Mao
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  10. Peter D. Stevens
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  11. Beth Schrope
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  13. James A. Lee
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  15. John A. Chabot
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Correspondence to Robert L. Fine.

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Fine, R.L., Gulati, A.P., Krantz, B.A. et al. Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience. Cancer Chemother Pharmacol 71, 663–670 (2013). https://doi.org/10.1007/s00280-012-2055-z

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